Do metastatic cancer tumours "break bad" or are they "born bad"?

This question is an essential mystery in cancer early detection and treatment.

Lacking a clear answer, patients are given the same aggressive therapies when small, abnormal clusters of cells are discovered early, even though they might well be harmless.

In a study publishing the week of May 14 in the Proceedings of the National Academy of Sciences, a research team co-led by scientists at Duke and the University of Southern California has found that in the colorectal tumours they examined, invasive cancers are born to be bad, and this tendency can potentially be identified at early diagnosis.

"We found evidence that benign and malignant tumours start differently, and that cell movement -- an important feature of malignancy -- manifests itself very early on during tumour growth," said lead author Marc D. Ryser, Ph.D., postdoctoral fellow in Duke's departments of Surgery and Mathematics.

"By testing screen-detected, small tumours for early cell movement as a sign of malignancy, it might be possible to identify which patients are likely to benefit from aggressive treatment," Ryser said.

Ryser and colleagues built on recent research showing that in a subset of human cancers, many key traits of the final tumour are already imprinted in the genome of the founding cell.

As such, they reasoned, invasive tumours would start out with the ability to spread rather than developing that trait over time.

That is, they are born to be bad.

The researchers analysed 19 human colorectal tumours with genome sequencing technology and mathematical simulation models.

They found signatures of early abnormal cell movement in the majority of the invasive samples -- nine of 15.

This propensity is required for tumours to spread, causing them to become deadly.

Early abnormal cell movement was not apparent in the four benign tumours the researchers studied.

"The early growth of the final tumour largely depends on the drivers present in the founding cell," the authors wrote.

The study was small and the researchers acknowledged that verification in a larger sample is required, but the finding is a significant step toward establishing a test to distinguish between deadly and harmless growths.

"Thanks to improved screening technologies, we diagnose more and more small tumours," said senior author Darryl Shibata, M.D., professor in the Department of Pathology at Keck School of Medicine of USC.

"Because treating a patient aggressively can cause them harm and side-effects, it is important to understand which of the small screen-detected tumours are relatively benign and slowly growing, and which ones are born to be bad."

Source: Duke University School of Medicine